Prostate carcinoma tumor size in rats decreases after administration of antagonists of luteinizing hormone-releasing hormone.
The effects of two potent antagonistic analogues of luteinizing hormone-releasing hormone (LH-RH) on the growth of two different models of rat prostate tumors have been investigated. Chronic administration of [NAc-p-F-DPhe1,p-Cl-DPhe2,DTrp3.6,D-Ala10]LH-RH (antagonist I) at 50 micrograms/day for 21 days significantly inhibited the growth of the chemically induced squamous cell carcinoma 11095 in Fisher 344 male rats. The weights of the pituitary, ventral prostate, and testes were not significantly altered. After 21 days of treatment with this analogue serum luteinizing hormone (lutropin), follicle-stimulating hormone, and testosterone levels were markedly decreased. When male Copenhagen F-1 rats bearing the Dunning 3327H prostate adenocarcinoma were injected with antagonist I at 50 micrograms/day for 6 weeks or with [NAc-p-Cl-DPhe1,2,DTrp3,DPhe6,DAla10]LH-RH (antagonist II) at 50 micrograms/day for 17 days, the percentage increase in tumor volume was decreased to half or less and the actual tumor volume was diminished 34-96% compared to controls. Tumor weight was decreased 30% and 89% after antagonist I and, respectively, compared to untreated controls. The tumor doubling time was 3- to 4-fold longer in rats receiving the inhibitory analogues than in the controls. Treatment with antagonist II decreased the weight of the whole prostate, but neither antagonist changed the weight of testes, anterior pituitary gland, or adrenals. Serum luteinizing hormone, follicle-stimulating hormone, and testosterone levels in Copenhagen F-1 rats bearing Dunning tumors were significantly decreased after treatment with the inhibitory analogues, but progesterone levels were increased. The inhibitory effects of these antagonistic analogues on rat prostate tumors suggest that these compound might be considered in the development of new types of therapy for prostate carcinoma and other endocrine-dependent neoplasias.
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D005640:Follicle Stimulating Hormone / Q000097:blood; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010903:Pituitary Gland, Anterior / Q000187:drug effects; D011471:Prostatic Neoplasms / Q000473:pathology*; D051381:Rats; D011916:Rats, Inbred F344; D013737:Testis / Q000187:drug effects; D013739:Testosterone / Q000097:blood; D013997:Time Factors
D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; C033850:LHRH, N-Ac-(4-F-Phe)(1)-(4-Cl-Phe)(2)-Trp(3,6)-AlaNH2(10)-; C033265:LHRH,(N)-Ac-(4-Cl-Phe)(1)-(4-Cl-Phe)(2)-Trp(3)-Phe(6)-AlaNH2(10)-; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone